The Pilot Research Project Core solicits, evaluates and supports new and innovative feasibility studies for the UIUC Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling. Our Core (and Center) are successful when we foster the success of promising young investigators new to either our `omics measurement capabilities or to addiction research, and we also encourage established researchers to explore new directions in addiction research. The selected pilot projects will have access to our considerable Center resources available through our scientific cores?Sampling and Separation, Molecular Profiling and Characterization, and Bioinformatics, Data Analytics and Predictive Modeling?to generate the data required for continued research and potential for longer-term support. The Center has worked with 38 users in the past, and the Pilot Research Project Core will ensure that this pipeline of innovative research and ideas continues to take advantage of the opportunities and expertise offered by our Center. Applicants who propose feasibility studies, who want to explore how to incorporate `omics data into their research, or what to start a new direction that fits the NIDA and Center research areas may qualify for support from the Pilot Core. To improve overall Center capabilities that will benefit multiple users, the Pilot Core will also support small technical, methodological, or conceptual developments from staff and users to improve Center measurement and informatics capabilities. Toward those goals, we outline three exemplary initial pilot projects targeting neuropeptides, transmitters, and proteins that are involved in multiple aspects of drug use. The first of the initial projects will address a longstanding question, the route of formation of endomorphin 2; the second project will seek to obtain an unprecedented level of chemical dimensionality and resolution in order to address individual neural plasticity and the influence of social environments while bringing an outstanding neuroscience team into the addiction research area; the third project will explore the mystery of co-transmission dynamics by hyphenating nanoelectrochemistry and mass spectrometry to explore how co-transmission affects neurotransmitter phenotype plasticity of neurons in relation to drug use. We will solicit new proposals each year, and support up to eight additional projects for competitive review by the Core over the next five years. The Core has a rigorous process in place to solicit, assess, and select Pilot Projects. Overall, the new Pilot Research Project Core is an important component of the UIUC Center for Neuroproteomics and Neurometabolomics on Cell-Cell Signaling.